The invention relates to novel hyperbranched dendrimers and polymers containing thiol functional groups, to a process for their preparation and to the use of these hyperbranched dendrimers and/or polymers as ancioxidants.
Many hyperbranched polymers and dendrimers have already been described. Reference may be made, for example to: D. A. Tomalia et al., Angew. Chem. Int. Engl. 29 (1990) 138-175; N. Ardoin and D. Astruc, Bull. Soc. Chim. Fr. (1995) 132, 875-909; B. I. Voit, Acta Polymer, 46, 87-99 (1995).
The possibility of preparing dendrimers containing thiol end groups has been envisaged by certain authors, such as, for example, D. A. Tomalia in U.S. Pat. No. 4,587,329 and EP-A-234,408, although this preparation has never been effectively carried out, nor have the surprising properties, demonstrated by the Applicant, of these molecules been mentioned or suggested in the prior art.
In addition, the process for preparing hyperbranched polymers and dendrimers containing thiol functional groups is novel and it has many advantages, among which are the good synthetic yield, the use of commercially available starting materials and the ease of implementation.
Hyperbranched polymers are molecular constructions having a branched structure, generally about a core. Their structure generally lacks symmetry: the monomer or base units involved in the construction of the hyperbranched polymer can be of varied nature and they are distributed non-uniformly. The branches in the polymer can be of varied nature and length. The number of base units, or monomers, can be different according to the different branching. While remaining asymmetrical, hyperbranched polymers can have: an extremely branched structure, around a core; successive generations or layers of branching; a layer of end chains.
Hyperbranched polymers are generally obtained from the polycondensation of one or more monomers ABx, A and B being reactive groups capable of reacting together, x being an integer greater than or equal to 2, but other preparation processes can be envisaged. Hyperbranched polymers are characterized by their degree of polymerization DP=1xe2x88x92b, b being the percentage of non-terminal functional groups in B which have not reacted with a group A. Since the condensation is non-systematic, in contrast with the synthesis of dendrimers, the degree of polymerization is less than 100%. Usually, by the known synthetic methods, DP is between 15 and 90%. An end group T can be reacted with the hyperbranched polymer to obtain a specific functionality at the end of the chains.
Such polymers are described in particular in B. I. Voit, Acta Polymer, 46, 87-99 (1995); EP-682,059, WO-96/14346; WO-96/14345; WO-96/12754.
Several hyperbranched polymers can be combined together, by means of a covalent bond or another type of bonding, via their end groups. Such so-called xe2x80x9cbridgedxe2x80x9d polymers come within the definition of the hyperbranched polymers according to the present invention.
Dendrimers are highly branched polymers and oligomers that are also known; they have a well-defined chemical structure and are said to be xe2x80x9cperfectxe2x80x9d hyperbranched polymers. As a general rule, dendrimers comprise a core, a determined number of generations of branches, or spindles, and terminal groups. The generations of spindles consist of structural units which are identical for the same generation of spindles and which can be identical or different for different generations of spindles. The generations of spindles extend radially in a geometrical progression from the core. The terminal groups of a dendrimer of the Nth generation are the terminal functional groups of the spindles of the Nth generation or terminal generation. Such polymers are described in particular in D. A. Tomalia, A. M. Naylor and W. A. Goddard III, Angewandte Chemie, Int. Ed. Engl. 29, 138-175 (1990); C. J. Hawker and J. M. J. Frechet, J. Am. Chem. Soc., 112, 7638 (1990); B. I. Voit, Acta Polymer, 46, 87-99 (1995); N. Ardoin and D. Astruc. Bull. Soc. Chim. Fr. 132, 875-909 (1995).
Dendrimers can also, more particularly, be defined by the formula (DI) below:
C[A1B1(A2B2( . . . (Anxe2x88x921Bnxe2x88x921(AnBn(T)rn)rxe2x88x921)rnxe2x88x922 . . . )r2)r1]sxe2x80x83xe2x80x83(DI)
in which:
C represents the core, linked by a number s of functional groups to s spindles A1B1 via the groups A1;
s is an integer greater than or equal to 1 and less than or equal to the number of functional groups in C;
for each spindle (AiBi) (i=1, 2 . . . n), the group Bi is linked to ri groups Ai+1 of a spindle (Ai+1Bi+1);
each group Ai (i greater than 2) is linked to a single group Bi+1 of the spindle (Ai+1Bi+1);
ri (i=1, 2 . . . nxe2x88x921) represents the number of functional groups in the group Bi belonging to the spindle (AiBi), ri being an integer greater than or equal to 2;
the index i (i=1, 2 . . . n) is an integer which denotes the generation of each spindle;
the spindle of nth generation AnBn is linked chemically to a number rn of terminal groups T, rn being an integer greater than or equal to zero.
The dendrimer definition given above includes molecules containing symmetrical branching; it also includes molecules containing non-symmetrical branching such as, for example, dendrimers whose spindles are lysine groups, in which the branching of one generation of spindles onto the preceding generation takes place on the amines a and e of lysine, which leads to a difference in the length of the spindles for the different branching.
Dense star polymers, starburst polymers and rod-shaped dendrimers are included in the present definition of dendrimers. The molecules known as arborols and cascade molecules also fall within the definition of dendrimers according to the present invention.
Several dendrimers can be combined together, via a covalent bond or another type of bond, via their terminal groups in order to give species known as xe2x80x9cbridged dendrimersxe2x80x9d or xe2x80x9cdendrimer aggregatesxe2x80x9d. Such species are included in the definition of dendrimers according to the present invention.
Dendrimers can be in the form of a set of molecules of the same generation, these being so-called monodispersed sets; they can also be in the form of sets of different generations, which are known as polydispersed sets. The definition of dendrimers according to the present invention includes monodispersed sets as well as polydispersed sets of dendrimers.
The subject of the invention is novel polymers chosen from hyperbranched polymers and dendrimers, characterized in that they contain functional groups corresponding to formula (I): 
in which:
Y represents an oxygen atom or an NH group, preferably Y=O,
A represents a linear, branched or cyclic, saturated or unsaturated C1-C12 alkanediyl group;
this alkanediyl group can optionally be interrupted by one or more hetero atoms, such as O or N;
this alkanediyl group can optionally be substituted with one of the following functions
amino: xe2x80x94NH2, optionally in the form of a salt of an inorganic or organic acid,
acylamino: xe2x80x94NHxe2x80x94COR, in which R represents a linear, branched or cyclic, saturated or unsaturated C1-C10 alkyl group,
carboxylic acid,
C1-C10 ester;
X represents a nucleophilic group, preferably:
an oxygen atom
or
a group xe2x80x94NRxe2x80x2xe2x80x94 in which Rxe2x80x2 is chosen from a hydrogen atom; a linear or branched, saturated or unsaturated C1-C6 alkyl group; a linear or branched, saturated or unsaturated C1-C6 mono- or polyhydroxyalkyl group; a C1-C6 aminoalkyl group or a polyalkyleneimine group.
For example, A can be a methylene, ethylene, propylene, methylpropylene, ethylpropylene, tetramethylene, pentamethylene, hexamethylene, phenylene, phenyldiyl, etc. group.
Advantageously, A represents a radical corresponding to one of the formulae (a) to (d) below:
xe2x80x94CHR1xe2x80x94CHR2xe2x80x94CHR3xe2x80x94xe2x80x83xe2x80x83(a)
xe2x80x94CHRxe2x80x21xe2x80x94CHRxe2x80x22xe2x80x94CHRxe2x80x23xe2x80x94CHRxe2x80x24xe2x80x94xe2x80x83xe2x80x83(b)
xe2x80x83xe2x80x94(CHRxe2x80x2xe2x80x31)kxe2x80x94(CHRxe2x80x2xe2x80x32) xe2x80x94CH(CO2H) xe2x80x94NHxe2x80x94xe2x80x83xe2x80x83(d)
in which R1, R2, R3, Rxe2x80x21, Rxe2x80x22, Rxe2x80x23, Rxe2x80x24, Rxe2x80x2xe2x80x31 and Rxe2x80x2xe2x80x32, which may be identical or different, represent: a hydrogen atom, a linear, branched or cyclic, saturated or unsaturated C1-C6 alkyl radical, an amino radical xe2x80x94NH2, a carboxylic acid radical xe2x80x94COOH, a C1-C10 alkylamino radical; Rxe2x80x31, Rxe2x80x32, Rxe2x80x33 and Rxe2x80x34, which may be identical or different, represent: a hydrogen atom, a linear or branched, saturated or unsaturated C1-C4 alkyl radical, the arrows indicating the positions of the substitutions in formula (c), k is an integer, preferably k=0 or 1.
Preferably, A is chosen from:
xe2x80x94CH2xe2x80x94CH (CO2H) xe2x80x94NHxe2x80x94 and Yxe2x95x90O
xe2x80x94(CH2)2xe2x80x94(CH3CONH) CHxe2x80x94 and Yxe2x95x90O
xe2x80x94(CH2)3xe2x80x94 and Yxe2x95x90O or Yxe2x95x90NH
Advantageously, A is the trimethylene radical xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94, and Yxe2x95x90O, the compound according to the invention corresponding in this case to formula (II) below: 
in which:
X represents a nucleophilic group, preferably:
an oxygen atom
or
a group xe2x80x94NRxe2x80x2xe2x80x94 in which Rxe2x80x2 is chosen from a hydrogen atom; a linear or branched, saturated or unsaturated C1-C6 alkyl group; a linear or branched, saturated or unsaturated mono- or polyhydroxyalkyl group; a C1-C6 aminoalkyl group or a polyalkyleneimine group.
Preferably, according to the invention, X is chosen from: an oxygen atom and an NH group.
In the case of dendrimers, the nucleophilic group X is generally an end functional group. In the case of hyperbranched polymers such as, for example, polyethyleneimine, the group X can be a secondary amine found on one of the branches of the polymer without being in the end position.
Advantageously, according to the invention, at least 10%, in numerical terms, of the groups X of the hyperbranched polymer or of the dendrimer are grafted with a functional group: 
and even more preferably at least 40%. The percentage of thiol functional groups relative to the total number of functional groups X in the hyperbranched polymer or the dendrimer which are capable of being substituted by a group: 
is adapted as a function of the other characteristics of the hyperbranched polymer or the dendrimer, in particular the number of generations and the nature of the spindles, and as a function of the expected properties, in particular the solubility of the hyperbranched polymer or of the dendrimer. Such adaptations are within the scope of a person skilled in the art by simple tests.
The subject of the invention is also a first process for preparing hyperbranched polymers and dendrimers containing thiol end groups, this process being characterized in that a starting polymer, chosen from hyperbranched polymers and dendrimers in which the end groups or chains contain a nucleophilic function, is reacted with a thiolactone or an iminothiolane according to the following reaction scheme: 
in which 
represents a dendrimer or a hyperbranched polymer containing n functions XH, as defined above, m is an integer m less than n and A represents a radical corresponding to one of the formulae (a) to (d) below:
xe2x80x94CHR1xe2x80x94CHR2xe2x80x94CHR3xe2x80x94xe2x80x83xe2x80x83(a)
xe2x80x94CHRxe2x80x21xe2x80x94CHRxe2x80x22xe2x80x94CHRxe2x80x23xe2x80x94CHRxe2x80x24xe2x80x94xe2x80x83xe2x80x83(b) xe2x80x83xe2x80x94(CHRxe2x80x2xe2x80x31)kxe2x80x94(CHRxe2x80x2xe2x80x32) xe2x80x94CH(CO2H) xe2x80x94NHxe2x80x94xe2x80x83xe2x80x83(d)
in which R1, R21, R3, Rxe2x80x21, Rxe2x80x22, Rxe2x80x23, Rxe2x80x24, Rxe2x80x2xe2x80x31 and Rxe2x80x2xe2x80x32, which may be identical or different, represent: a hydrogen atom, a linear or branched, saturated or unsaturated C1-C6 alkyl radical, an amino radical xe2x80x94NH2, a carboxylic acid radical xe2x80x94COOH, a C1-C10 alkylamino radical; Rxe2x80x31, Rxe2x80x32, Rxe2x80x33 and Rxe2x80x34, which may be identical or different, represent: a hydrogen atom, a linear or branched, saturated or unsaturated C1-C4 alkyl radical, the arrows indicating the positions of the substitutions in formula (c); k is an integer, preferably k=0 or 1.
Preferably, in the process according to the invention, the compound 
is chosen from:
2-oxo-4-thiazolidinecarboxylic acid, also known under the name procysteine: 
N-acetylhomocysteinethiolactone: 
xcex3-thiobutyrolactone: 
iminothiolane: 
Advantageously, in the process according to the invention, a reactant chosen from procysteine, N-acetylhomocysteinethiolactone and xcex3-thiobutyrolactone is used.
Advantageously, in the process according to the invention, the compound 
is xcex3-thiobutyrolactone.
xcex3-Thiobutyrolactone is a commercial product.
The reaction for opening the thiolactone or iminothiolane is generally carried out under inert atmosphere either in water or in an aromatic solvent such as toluene or an alcohol such as methanol, ethanol, isopropanol or butanol, and, depending on the boiling point of the solvent, at a temperature of between 0xc2x0 C. and 110xc2x0 C.
However, according to a preferred form of the invention, the reaction is carried out in water and, in this case, the dendrimer or the hyperbranched polymer and the thiolactone or the iminothiolane are mixed in stoichiometric proportions (relative to the functions xe2x80x94XH of the polymer) and the mixture is then brought, under inert atmosphere, to a temperature of between 0xc2x0 C. and 110xc2x0 C.
When it is desired to conserve the free amine or hydroxyl functions among the n functional groups of the hyperbranched polymer or of the dendrimer, the desired amount m of thiolactone or iminothiolane molecules per dendrimer molecule or per hyperbranched polymer molecule is used in order to obtain the dendrimer or the hyperbranched polymer having n-m free amine or hydroxyl functions and m thiol functions.
Depending on the basicity of the dendrimer or the hyperbranched polymer, the reaction time can be between 1 and 48 hours, the reaction progress being monitored by assaying the appearance of the thiol and/or the disappearance of the amine function or of the alcohol function. It is also possible to monitor the conversion of the starting polymer by electrophoresis.
Advantageously, when the radical xe2x80x94Axe2x80x94 contains a free acid function or a free amine function, this function is neutralized before introducing the starting polymer into the reaction medium.
If, during the reaction, a certain amount of thiol is oxidized into the corresponding disulphide, the reaction mixture is then diluted with twice its volume of water and stirred in acidic medium in the presence of zinc powder for 1 to 3 hours. With most of the disulphide having been reduced, the mixture is then filtered and a solution of the expected compound is obtained, which can be used directly.
Dendrimers and hyperbranched polymers containing a mercaptoalkylamide function can also be obtained in a known manner by an amidation reaction of the corresponding mercaptoalkanoic acid or esters thereof. Such a process can be represented by the following reaction scheme: 
in which X, n, m, A and 
have the same meaning as above and Q represents a hydrogen atom or a saturated or unsaturated, linear or branched C1-C10 alkyl radical.
However, the preparation process described above starting with a thiolactone or an iminothiolane is faster and does not lead to the formation of side products that occasionally have a very unpleasant odour and contaminate the final product.
Reference may be made to the following documents which describe hyperbranched polymers and dendrimers in which the terminal group contains an amine function, the content of these documents being incorporated into the present description by reference: U.S. Pat. No. 4,694,064; U.S. Pat. No. 4,507,466; U.S. Pat. No. 4,631,337; U.S. Pat. No. 4,558,120; U.S. Pat. No. 4,568,737; U.S. Pat. No. 4,587,329; WO-A-9502008; WO-A-9314147; EP-234408; U.S. Pat. No. 4,289,872; U.S. Pat. No. 4,360,646; Proc. Natl. Acad. Sci. USA, 85, 5409-5413 (1988); WO95/02008; WO93/14147; J. Am. Chem. Soc. 117, 9764 (1195); FR-2,734,268.
Dendrimers containing terminal groups bearing a primary amine function are polyamidoamines such as those sold under the trade name Starburst PAMAM by the company Dendritech (block copolymers of ethylenediamine and of methyl acrylate). They can also be chosen from polyalkylenepolyamine-type dendrimers such as, for example, the polyethyleneimines and polypropyleneimines manufactured by the company DSM and described in the patents: WO 93/14147 and WO 95/02008. They may also belong to the polylysine family, as described in U.S. Pat. No. 4,360,646. Among the hyperbranched polymers, mention may be made of polyalkylenepolyamines such as the polyethyleneimine sold by the company BASF under the brand names Polymin and Lupasol.
Hyperbranched polymers and dendrimers containing amine functional groups can also consist of a core and generations of base units, monomers or spindles, of any nature, on which an end group T bearing an amine function has been grafted.
Hyperbranched polymers and dendrimers containing hydroxyl end groups, in particular polymers of the polyester family, are described in the following documents, the content of which is incorporated into the present description by reference: U.S. Pat. No. 4,587,329; WO 93/17060; WO 92/14543; J. Am. Chem. Soc., 113, 4583-4588 (1991); Macromolecules 25, 4583-4587 (1992); U.S. Pat. No. 5,196,502; U.S. Pat. No. 5,214,122.
Preferably, the starting polymer is chosen from dendrimers.
After the reaction, the nature of the core and the branches of the starting polymer are not modified. Possibly, as a function of the proportions of reactants used, some of the starting end groups are not modified. Thus, if a polyamidoamine is used to begin with, which is treated with xcex3-thiobutyrolactone, the process of the invention gives a polyamide containing mercapto-4-butyramide end functions. Starting with a polyalkylenepolyamine, the process of the invention gives a polyalkylenepolyamine grafted with mercapto-4-butyramide functional groups. Starting with a polyester, the process of the invention gives a polyester containing mercapto-4-butyramide end functions.
These novel polymers have reductive properties and can be used in place of the reducing agents used conventionally, for example in cosmetic applications, such as, for example, treatment of the nails and the hair. In particular, these novel polymers can be used as reducing agents in permanent-waving compositions.
Since the polymers according to the invention contain an xe2x80x94SH end function, they can be used as preserving agents for protecting products that are particularly sensitive to oxidation. They can be used as antioxidants in compositions of any nature, especially in cosmetic or pharmaceutical compositions, for example in hair compositions, as shampoos, lotions, gels, emulsions or lacquers for the hair, rinse-out compositions, to be applied before or after shampooing, before or after dyeing or bleaching, before, during or after permanent-waving or straightening of the hair, styling or treating lotions or gels, lotions or gels for blow-drying or setting the hair, and permanent-waving, straightening, dyeing or bleaching compositions for the hair. They can also be used as antioxidants in skincare products or make-up products, such as products for making up the eyelashes, the eyebrows or the skin, such as an epidermal treatment cream, a foundation, a lipstick, an eyeshadow, a blusher, a mascara, an eyeliner or a nail varnish, or in skincare or skin cleansing lotions, creams and milks.
The subject of the invention is also a composition comprising, in a cosmetically or dermatologically acceptable support, at least one polymer according to the invention.
When applied to a support, the polymers according to the invention can form a film resulting from the formation of intermolecular disulphide bridges, thus leading to a polymer of the dendrimer or of the hyperbranched polymer containing xe2x80x94SH end functions.
This film can be formed from a few thiol functions, the other functions remaining free and being capable of having a reductive action.
The use of the polymers according to the invention as antioxidants can be envisaged directly in solution in the medium to be protected from oxidation, as is common with standard antioxidants such as thioglycolic acid, thiolactic acid or cysteine.
If the polymer is insoluble in the medium to be protected from oxidation, it is also possible to envisage fixing it, for example, in the form of a film or a pellet, to the walls or into the stopper of the bottle containing the formulation to be protected.
In this second case, the dendrimer or the hyperbranched polymer according to the invention can also be combined with a small amount of one of the mercaptans usually used as antioxidant, such as, for example, thioglycolic acid, thiolactic acid or cysteine. This combination thus makes it possible to limit the amount of soluble thiol in the composition to be protected and hence the usual drawbacks associated therewithxe2x80x94odour, changing of the colourxe2x80x94while at the same time retaining remarkable efficacy. The subject of the invention is thus also such a combination.
The hyperbranched polymers and dendrimers according to the invention have in particular the advantage of having a much fainter odour than the thiols usually used as antioxidantsxe2x80x94they are virtually odourless at room temperature.
On account of their specific structure, the hyperbranched polymers and dendrimers according to the invention penetrate very little into keratin or into the epidermis, and they are thus relatively non-sensitizing and pose no toxicity problems.